Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study.

BACKGROUND: The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019). PATIENTS AND METHODS: Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety. RESULTS: Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32-0.58; median PFS 34.8 versus 10.9 months crizotinib]. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46-0.98). The 5-year OS rate was 62.5% (95% CI 54.3-70.8) with alectinib and 45.5% (95% CI 33.6-57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline [HR 0.58 (95% CI 0.34-1.00)] and those without [HR 0.76 (95% CI 0.45-1.26)]. Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed. CONCLUSIONS: Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC. CLINICAL TRIALS NUMBER: NCT02075840.

[Evaluation of mitral regurgitation : How much quantification do we need?] / Diagnostik der Mitralinsuffizienz : Wie viel und welche Quantifizierung brauchen wir?

Severe mitral regurgitation (MR) is associated with increased morbidity and mortality. Thus, the correct evaluation of the underlying etiology, pathomechanism and severity is crucial for optimal treatment. Echocardiography is the predominant diagnostic modality in the clinical routine as it enables grading of mitral regurgitation, which can frequently be achieved by readily available qualitative parameters. Additionally, echocardiography provides several methods to quantify the hemodynamic significance of MR. The effective regurgitation orifice area (EROA) is the quantitative parameter best correlated with clinical events. American and European imaging guidelines both recommend the use of quantitative parameters even though they disagree on the cut-off values for secondary MR. The evaluation of MR should always include an assessment of the adjacent heart chambers in order to be able to assess the impact of volume overload on size and function of the left ventricle and left atrium. The final interpretation of the quantitative parameters requires knowledge of left ventricular volume and ejection fraction. Newer 3D-echocardiographic approaches to quantify MR are less dependent on mathematical assumptions and have shown convincing results in several studies but still lack sufficient clinical validation. As an alternative to echocardiography, for specific indications cardiac magnetic resonance imaging (MRI) has proven to be a systematic and observer-independent method for quantification of MR.

Expert proposal to analyze the combination of aortic and mitral regurgitation in multiple valvular heart disease by comprehensive echocardiography.

The assessment of valvular pathologies in multiple valvular heart disease by echocardiography remains challenging. Data on echocardiographic assessment-especially in patients with combined aortic and mitral regurgitation-are rare in the literature. The proposed integrative approach using semi-quantitative parameters to grade the severity of regurgitation often yields inconsistent findings and results in misinterpretation. Therefore, this proposal aims to focus on a practical systematic echocardiographic analysis to understand the pathophysiology and hemodynamics in patients with combined aortic and mitral regurgitation. The quantitative approach of grading the regurgitant severity of each compound might be helpful in elucidating the scenario in combined aortic and mitral regurgitation. To this end, both the individual regurgitant fraction of each valve and the total regurgitant fraction of both valves must be determined. This work also outlines the methodological issues and limitations of the quantitative approach by echocardiography. Finally, we present a proposal that enables verifiable assessment of regurgitant fractions. The overall interpretation of echocardiographic results includes the symptomatology of patients with combined aortic and mitral regurgitation and the individual treatment options with respect to their individual risk. In summary, a reproducible, verifiable, and transparent in-depth echocardiographic investigation might ensure consistent hemodynamic plausibility of the quantitative results in patients with combined aortic and mitral regurgitation.

Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib.

Alectinib is a preferred first-line therapy for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in several national clinical practice guidelines. The randomized, global, phase III ALEX study has demonstrated significant improvement in progression-free survival for alectinib over crizotinib in treatment-naive ALK-positive NSCLC. It was also the first study to show clinically meaningful improvement in overall survival for a next-generation ALK tyrosine kinase inhibitor relative to crizotinib. The J-ALEX and ALESIA phase III studies confirmed the clinical benefit of alectinib relative to crizotinib in the first-line ALK-positive NSCLC treatment setting in Japanese and Asian patients, respectively. Across these pivotal phase III trials, alectinib had a manageable, well-characterized safety profile. Here, we review the safety and tolerability of long-term alectinib treatment in patients with advanced ALK-positive NSCLC and provide guidance for physicians, based on clinical experience, on the management of the most frequently reported adverse events (AEs). Most AEs associated with alectinib can be managed by dose reduction. Some alectinib-related AEs are not yet fully characterized, including myalgia and peripheral oedema and deciphering their underlying mechanism of action could enhance their management. With longer-term follow-up, the safety profile of alectinib continues to remain consistent in the ALEX study, with no new safety signals observed. Safety and tolerability data from the first-line phase III alectinib trials are also consistent with those observed in clinical trials of alectinib in later-line settings. These results add to the weight of evidence recommending alectinib as a preferred therapy for treatment-naive advanced ALK-positive NSCLC.

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer.

BACKGROUND: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling. PATIENTS AND METHODS: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes. RESULTS: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93). CONCLUSIONS: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.

Peak energy turnover in lactating European hares: a test of the heat dissipation limitation hypothesis.

It has been suggested that maximum sustained metabolic rate (SusMR) in mammals as reached, for instance, during lactation, is due to a limited capacity for heat dissipation. Here, we experimentally tested whether heat dissipation limitation (HDL) also constrains energy turnover in lactating European hares. Experimentally, we made use of the fact that hares nurse their young only once per day, which allowed us to keep females and young either at the same or at different ambient temperatures. During the last lactation week (week 4) females kept at thermoneutrality (22 degrees C), irrespective of the cold load of their young, had significantly lower rates of metabolisable energy intake (MEI) than cold-exposed mothers (5 degrees C), as predicted by the HDL hypothesis. However, in week 2 of lactation females at thermoneutrality rearing cold-exposed young were able to increase MEI to levels indistinguishable from those of cold-exposed females. Thus, even at thermoneutral temperature females reached maximum rates of energy turnover, which was inconsistent with the HDL hypothesis. We conclude that SusMR in lactating European hares typically results not from physiological constraints but from an active restriction of their energy turnover in order to maximise lifetime reproductive success.

Eritema multiforme, una rara presentación de exantema en población pediátrica: a propósito de un caso / Erythema multiforme, a rare occurrence of exanthema in the pediatric population: on the subject of a case

El Eritema multiforme (EM) o eritema polimorfo es una enfermedad aguda de la piel de naturaleza inmunológica con o sin compromiso de mucosas, que puede comportarse como crónica recurrente. Se presenta con lesiones cutáneas en diana distintivas, a menudo acompañado de úlceras o bullas en mucosas (oral, genital u ocular). Entre sus formas clínicas se distingue: una forma menor caracterizado por un síndrome cutáneo leve y su forma mayor que se manifiesta como una afectación cutánea con daño mucoso marcado. Entre sus principales diagnósticos diferenciales se encuentran el Síndrome de Stevens-Johnson (SSJ) y Síndrome de Lyell (Necrólisis epidérmica tóxica (NET)). Tiene una incidencia estimada < 1%, siendo su forma mayor levemente más frecuente que su forma menor (0.8-6 por millón/año). Puede darse a cualquier edad, presentando un peak de incidencia entre los 20 y 30 años, predominando ligeramente el sexo masculino con una proporción 3:2, sin predilección racial. Su presentación en edad pediátrica es rara, más aún en la primera infancia. En esta población es más frecuente el EM menor recurrente. En el presente texto se reporta un caso de EM en población pediátrica como una rara forma de presentación exantemática, abordado en el Servicio de Pediatría del Complejo Asistencial Dr Victor Rios Ruiz (CAVRR)en la ciudad de Los Ángeles, Chile en el presente año.

Erythema multiforme (EM) also known as polymorph erythema is an acute skin disease of immunological nature with or without mucous membrane involvement, which may behave as chronic recurrent. It presents with distinctive targets like skin lesions, often together with ulcers or bullae in mucous membranes (oral, genital or ocular). Among its clinical forms are: a minor form characterized by a mild skin syndrome and its major form that manifests as a skin disease with marked mucosal damage. Among its main differential diagnoses are Stevens-Johnson Syndrome (SJS) and Lyell Syndrome (Toxic Epidermal Necrolysis (TEC)). It has an estimated incidence < 1%, with its major form being slightly more frequent than its minor form (0. 8-6 per million/year). It can occur at any age, presenting a peak incidence at the age between 20 and 30 years, with a slight predominance of males with a 3:2 ratio, without racial predilection. Its presentation in pediatric age is rare, even more so in early childhood. Minor recurrent EM is more common in this population. This paper reports a case of EM in the pediatric population as a rare form of exanthematic presentation, addressed at the Department of Pediatrics of the Complejo Asistencial Victor Rios Ruiz (CAVRR) in the city of Los Angeles, Chile this year.

Effects of polystyrene nanoparticles on the microbiota and functional diversity of enzymes in soil.

BACKGROUND: The increasing production of nanoplastics and the fragmentation of microplastics into smaller particles suggest a plausible yet unclear hazard in the natural environment, such as soil. We investigated the short-term effects (28 days) of polystyrene nanoparticles (PS-NPs) on the activity and biomass of soil microbiota, and the functional diversity of soil enzymes at environmental relevant low levels in an incubation experiment. RESULTS: Our results showed a significant decrease in microbial biomass in treatments of 100 and 1000 ng PS-NP g-1 DM throughout the incubation period. Dehydrogenase activity and activities of enzymes involved in N-(leucine-aminopeptidase), P-(alkaline-phosphatase), and C-(ß-glucosidase and cellobiohydrolase) cycles in the soil were significantly reduced at day 28 suggesting a broad and detrimental impact of PS-NPs on soil microbiota and enzymes. Leucine-aminopeptidase and alkaline-phosphatase activities tended to decrease consistently, while ß-glucosidase and cellobiohydrolase activities increased at high concentrations (e.g., PS-NP-1000) in the beginning of the incubation period, e.g., at day 1. On the other hand, basal respiration and metabolic quotient increased with increasing PS-NP application rate throughout the incubation period possibly due to increased cell death that caused substrate-induced respiration (cryptic growth). CONCLUSIONS: We herewith demonstrated for the first time the potential antimicrobial activity of PS-NPs in soil, and this may serve as an important resource in environmental risk assessment of PS-NPs in the soil environment.

High survival in poor years: life history tactics adapted to mast seeding in the edible dormouse.

Edible dormice (Glis glis) reproduce in years with beech mast seeding, but entire populations may skip reproduction in years when tree seeds, a major food resource of this small hibernator, are absent. We tested the hypothesis that the year-to-year variability in reproductive effort caused by this breeding strategy should lead to detectable differences in yearly survival rates. Therefore, we analyzed capture-recapture data from animals occupying nest boxes, collected over nine years at two study sites in Germany. Among fully grown adults (aged two years or older), survival probabilities were significantly lower (0.32 +/- 0.04) after reproductive years (n = 5) compared to years (n = 4) with absent or below-average reproduction (0.58 +/- 0.07) on both study sites. This trade-off between reproduction and subsequent survival was observed in both females and males and appears to be a relatively rare case in which costs of reproduction in terms of longevity are detectable at the population level. Effects of reproduction on survival were less pronounced when yearlings (with a generally lower reproductive effort) were included and were more distinct in a suboptimal habitat. Of those females breeding in nest boxes, 96.5% had only one or two litters within the study period. Considering these and previously published results, including a report of extremely high mean longevities (9-12 years) of dormice in a habitat with infrequent mast seeding, we conclude that edible dormice flexibly adjust life history tactics to local mast patterns. Long stretches of mast failures can in fact lead to relative semelparity, i.e., a strategy in which dormice "sit tight" for several years until environmental conditions are favorable for reproduction.

Photoperiod and thermoregulation in vertebrates: body temperature rhythms and thermogenic acclimation.

Evidence has recently begun to accumulate that photoperiodic responses of mammals and birds may affect the control of energy balance and thermoregulation. Exposure to short photoperiod can lower the set point for body temperature regulation in birds and mammals, as well as the voluntarily selected body temperature in ectothermic lizards. This decrease is accompanied by a reorganization of circadian or ultradian rhythms of body temperature, particularly an increase in periods spent at rest with minimum body temperatures. Short photoperiod is also used as an environmental cue for induction of seasonal torpor or facilitation of hibernation. During winter, cold tolerance of small mammals is improved by an increase of nonshivering thermogenesis in brown fat. Thermogenic capacity of brown fat (respiratory enzymes, mitochondria, uncoupling protein) is enhanced in response to short photoperiod. This response is mediated via an increase in the activity of sympathetic innervation in brown fat. Moreover, an exposure to short photoperiod prior to low temperatures may act in preparing brown fat for facilitated thermogenesis during acclimation to cold. This shows that photoperiodic control not only affects energy balance indirectly via the control of reproduction or body mass, but may directly interact with central control of thermoregulation and may influence the process of acclimatization.

Modulation of myocardial economy and efficiency in mammalian failing and non-failing myocardium by calcium channel activation and beta-adrenergic stimulation.

OBJECTIVE: We investigated the energy-metabolic consequences of positive inotropic stimulation by the calcium channel activator, BAY K 8644, in comparison with isoprenaline, focussing both on the economy of force development and the efficiency of external work. METHODS: In the first instance, heat liberation was measured in isometrically contracting right ventricular papillary muscles from guinea pigs by means of antimony-bismuth thermopiles; in the second instance, external work and myocardial oxygen consumption were analyzed in isolated failing and non-failing working rat hearts. RESULTS: In the guinea pig muscle strip preparations BAY K 8644 (10(-5) M) and isoprenaline (10(-8 M) increased peak developed force from 13.7 +/- 2.7 to 37.6 +/- 14.9 mN/mm2 and from 13.6 +/- 5.2 to 38.8 +/- 3.3 mN/mm2, respectively (P < 0.01). Stress-time integral was increased from 10.3 +/- 3.0 to 34.7 +/- 19.2 mN.s/mm2 by BAY K 8644 and from 9.5 +/- 2.4 to 23.0 +/- 1.6 mN.s/mm2 by isoprenaline. Whereas a significant decrease in the ratio between stress-time integral and initial heat (integral of Pdt/IH) (i.e., economy contraction) was observed for isoprenaline (5.26 +/- 1.91 before and 3.11 +/- 0.72 N.m.s.J-1 after treatment (P < 0.01), BAY K 8644 did not significantly alter this index (5.26 +/- 2.39 before and 6.22 +/- 2.63 N.m.s.J-1 after treatment). Similar results were obtained for the ratio between stress-time integral and tension-dependent heat. Significantly more calcium ions were required for equieffective activation of the contractile proteins with isoprenaline as compared to BAY K 8644. In working preparations of sham-operated and infarcted rat hearts, the increase in myocardial oxygen consumption per minute (delta MVO2) for a given increase in external work per minute (delta P) was significantly higher with isoprenaline than with equipotent concentrations of BAY K 8644 or high calcium. CONCLUSIONS: Inotropic mycardial stimulation by BAY K 8644 is associated with higher economy and efficiency than stimulation by isoprenaline when analyzed both by heat measurements in isometric preparations and by myocardial oxygen consumption in working heart preparations.

Alterations of cross-bridge kinetics in human atrial and ventricular myocardium.

CONDENSED ABSTRACT: We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricular human myocardium. beta-Adrenergic stimulation increased the minimum stiffness frequency by 18 +/- 3% (p < 0.05). Cross-bridge kinetics are temperature-dependent, with a Q10 of at least 2.7. BACKGROUND: Dynamic stiffness measurements have revealed acute and chronic alterations of actomyosin cross-bridge kinetics in cardiac muscles of a variety of different animal species. We studied dynamic stiffness in right atrial and left ventricular preparations of non-failing and failing human hearts and tested the influence of the temperature and beta-adrenergic stimulation on cross-bridge kinetics. METHODS AND RESULTS: Muscle strips were prepared from right atria and left ventricles from human non-failing and failing hearts. After withdrawal of calcium, steady contracture tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length oscillations of 1% muscle length were applied, with a frequency spectrum of between 0.1 and 60 Hz. Dynamic stiffness was calculated from the length change and the corresponding force response amplitude. The specific minimum stiffness frequency, which indicates the interaction between cross-bridge recruitment and cross-bridge cycling dynamics, was analyzed for each condition: (1) The minimum stiffness frequency was 0.78 +/- 0.04 Hz in left ventricular myocardium and 2.80 +/- 0.31 Hz in right atrial myocardium (p < 0.01) at 27 degrees C. (2) The minimum stiffness frequency was 41% higher in non-failing compared to failing left ventricular human myocardium. (3) Over a wide range of experimental temperatures, the minimum stiffness frequency changed, with a Q10 of at least 2.7. (4) beta-Adrenergic stimulation significantly (p < 0.05) increased the minimum stiffness to 18 +/- 3% higher frequencies and significantly (p < 0.05) lowered contracture tension by 7 +/- 1%. CONCLUSIONS: The contractility of human heart muscle is not only regulated by excitation-contraction coupling but also by modulation of intrinsic properties of the actomyosin system. Acute and chronic alterations of cross-bridge kinetics have been demonstrated, which play a significant role in the physiology and pathophysiology of the human heart.

Shortening versus isometric contractions in isolated human failing and non-failing left ventricular myocardium: dependency of external work and force on muscle length, heart rate and inotropic stimulation.

BACKGROUND: For reasons of simplicity, studies on isolated human myocardium have been conducted using exclusively isometric contractions, although positive inotropic interventions may differently influence force development, extent of shortening and myocardial work performance. We investigated human left ventricular failing and non-failing preparations comparing isometric versus isotonic, i.e., shortening contractions. RESULTS: (1) When muscle length is increased from 90% to 100% lMAX, peak developed force increases by 36% and 43% (p < 0.05) in non-failing and failing human left ventricular myocardium, respectively. Maximum performed work increases similarly in non-failing but decreases in failing myocardium. It can be shown that this discrepancy is due to significantly higher resting tension and does not present an insufficient intrinsic shortening capacity in failing myocardium. (2) When stimulation rate is increased from 0.5 to 2.0 Hz, isometric force increases significantly by 59% in non-failing and decreases by 27% in failing myocardium, whereas maximum performed work increases by 98% and decreases by 46%, respectively. (3) Pharmacological positive inotropic interventions by 7.2 mM calcium (n = 9), 3 x 10(-8) M isoproterenol (n = 7), 3 x 10(-8) M ouabain (n = 5), and 10(-5) M EMD 57033 (n = 3) equally increased force development and extent of shortening: When the fractional effect on shortening (y) was correlated to the fractional effect on force (x), the following linear regression equation was obtained: y = 0.91x + 0.26 (r = 0.86; p < 0.001). CONCLUSIONS: The data presented are of clinical and pharmacological importance: (1) The Frank-Starling mechanism is demonstrated to be existent in the failing human myocardium regarding both isometric force developed and maximum work performed. (2) Both force-frequency relations and--to a greater extent--work-frequency relations are reversed in failing human myocardium. (3) Independent of the pharmacological mode of action, positive inotropic compounds increase developed isometric force to the same extent as isotonic shortening and therefore potentiate maximum performed work.

Virus-like particles in a case of acute hepatitis with human GB virus-C viraemia.

BACKGROUND/AIMS: It is still controversial whether the human GB virus-C can cause liver injury, as in situ demonstration of the virus is still inconclusive. METHODS: Here we describe the case report of a patient with two episodes of severe acute hepatitis, who had a meticulous clinical, immunological and microbiological work-up, including human GB virus-C RNA detection by in situ hybridization and electron microscopy. RESULTS: Human GB virus-C viraemia was found as the only potential cause of hepatitis in this patient. Furthermore, virus-like particles could be demonstrated in the cytoplasm of single hepatocytes by electron microscopy and human GB virus-C RNA was detected in the liver by in situ hybridization. CONCLUSION: The presence of human GB virus-C RNA in serum together with the demonstration of human GB virus-C RNA in the liver, favour acute human GB virus-C infection as the cause of liver injury in this patient. Thus virus-like particles and hepatic human GB virus-C RNA should be specifically looked for by electron microscopy and in situ hybridization, especially during the diagnostic work-up of patients with unexplained hepatitis.

Serum levels of immunoreactive bone sialoprotein in osteoporosis: positive relations to established biochemical parameters of bone turnover.

Bone Sialoprotein (BSP), synthesized by osteoblasts and osteoclasts, is a highly glycosylated and phosphorylated protein, accounting for approximately 5-10% of noncollagenous proteins of bone extracellular matrix. The present study investigates possible correlations between serum values of immunoreactive Bone Sialoprotein in relation to established bone turnover markers like osteocalcin (OC), bone alkaline phosphatase (B-ALP) and the c-terminal extension peptide of type-I-Procollagen (PICP) in 170 osteoporosis patients (female n = 144, male n = 26) in order to evaluate the usefulness of BSP in the diagnosis of bone disease. Fasting venous blood samples were collected from our osteoporosis outpatients in the morning and stored at -80 degrees C until processing. Serum levels of BSP were determined by RIA, OC and B-ALP were measured by IRMA, and PICP was assessed employing an ELISA technique. A significant correlation was found between BSP serum values and B-ALP (r = 0.532, p = 0.0001). Median serum BSP levels were 8.0 micrograms/l, median B-ALP values were 22.39 U/ml in these patients. Also a significant correlation was observed between BSP and OC (r = 0.588, p = 0.0001), more pronounced in the female patient group (r = 0.632, p < 0.0001). A weak association between BSP and PICP in the female group was detected (r = 0.398, p = 0.0001). In the female group BSP was inversely related to serum estradiol levels (r = -0.274, p = 0.002) as to BMD (DEXA) at the lumbar spine and femoral neck. In conclusion, BSP might be a useful marker of non-collagenous organic bone matrix in laboratory assessment of bone turnover, being inversely related to BMD at lumbar spine and femoral neck and showing significant correlations to established markers of bone turnover like B-ALP and OC.

Computerized body temperature telemetry in small animals: use of simple equipment and advanced noise suppression.

Telemetric measurement of body temperatures in small animals implanted with commercially available transmitters (Mini-Mitter) has been automated using the Commodore C-64 microcomputer. Transmitter output frequencies are received by common AM-radios, converted to TTL level by a simple interface and measured by a machine language subroutine. Multiplexed input is under software control and allows for the recording of at least 16 animals selectively, with data points for each sample every 3 min. The effects of environmental electrical noise are significantly reduced by an error detection system based on the separate reception of interference.

Effects of season and reproductive state on lipid intake and fatty acid composition of gastrointestinal tract contents in the European hare.

We investigated lipid content and fatty acid (FA) composition of gastrointestinal tract contents in free-living, herbivorous European hares (Lepus europaeus). Mean crude fat content in hare stomachs and total gastrointestinal (GI) tracts was higher than expected for typical herbivore forages and peaked in late fall when hares massively deposited body fat reserves. Changes of FA proportions in different parts of the GI-tract indicated a highly preferential absorption of polyunsaturated fatty acids (PUFA). A further reduction of PUFA content in the caecum, along with the appearance of odd-chained FAs in caecum, caecotrophes, and colon content, pointed to a biohydrogenation of PUFA in the hare's hindgut. GI-tract contents showed significant seasonal changes in their FA composition. Among PUFA, α-linolenic acid peaked in spring while linoleic acid was predominant in late summer and fall, which probably reflected changes in the plant composition of forage. However, independent of seasonal changes, GI-tracts of lactating females showed a significantly (+33%) higher content of linoleic acid, a FA that is known to increase reproductive performance in European hares. This finding suggests that lactating females actively selected dietary plants rich in linoleic acid, a PUFA that may represent a limited resource for European hares.